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Abstract Sugar beverages are discussed as critical in the development of metabolic endotoxemia. Here, employing a cross-over design study we assessed the effect of diluted cloudy apple juice (AJ), an iso-caloric and -sweetened placebo (P), or water (W) on post-prandial endotoxemia in healthy, normal weight adults. After obtaining fasting blood, 19 healthy men and women consumed 500 mL AJ, P, or W in a randomized order and blood was taken 120 and 180 min later. Caco-2 cells were incubated with the beverages. Markers of intestinal barrier function were assessed. The intake of P but not of AJ or W was associated with a significant increase in TLR2 ligands and bacterial endotoxin in serum after 120 min and 180 min, respectively. P but not AJ significantly increased bacterial toxin permeation in Caco-2 cells. Our results suggest that the effects of sugar-sweetened beverages on markers of intestinal barrier function markedly differ from those of fruit juices.

At the time of writing, in the summer of 2024, we are confronted with a ‘polycrisis’ (e.g., Tooze 2022). This term is used to describe a situation in which multiple crises do not simply add up to a somewhat bigger crisis, but rather create a significantly different, amplified crisis in which the sub-crises influence each other in interdependent ways. As numerous studies have demonstrated (e.g., Heitmeyer 2024; Roberts 2022; Nowotny 2016), crises engender feelings of uncertainty, insecurity, and subsequently fear (Bauman 2006). The aim of this paper is to pose the overarching question: How do governments and citizens cope with such uncertainties? Les crises provoquent la peur, la panique, l’incertitude et l’impuissance. L’incertitude et l’insécurité mettent à l’épreuve tous les acteurs concernés ; chacun attend des instructions, une planification, des explications et la sécurité. Cependant, nous affrontons des alarmismes, des simplifications, une série de stratégies de légitimation et d’erreurs. Plus précisément, les erreurs sont souvent placées avant les intérêts communautaires, nationaux ou même locaux. Ces évolutions sont illustrées par une analyse qualitative et quantitative détaillée du discours des débats en Autriche, à l’été 2023. Je soutiens que les appels fallacieux au bon sens et à la normalité dépendent de leur contexte, avec des contenus, des fonctions et des effets différents observables. De tels appels instrumentalisent une « politique des émotions » de différentes manières. Ainsi, une nouvelle logique politique est normalisée, remplaçant le discours rationnel, la délibération et la formulation de politiques dirigées par des experts.

Background & Aims: Changes in phosphatidylcholine levels in the liver have been associated with the development of metabolic dysfunction–associated steatotic liver disease. Here, the effects of supplementing phosphatidylcholine on the development of early signs of metabolic dysfunction–associated steatohepatitis were assessed. Methods: Male and female C57BL/6J mice were fed a liquid control or a fructose-, fat-, and/or cholesterol-rich diet for 7 or 8 weeks. The diets of female mice were fortified ± phosphatidylcholine (12.5 mg/g diet). In liver tissue and portal blood, indices of liver damage, inflammation, and bacterial endotoxemia were measured. J774A.1 cells and human monocytes preincubated with phosphatidylcholine (0.38 mmol/L) were challenged with lipopolysaccharide (50–100 ng/mL) ± the peroxisome proliferator-activated receptor γ (PPARγ) activator pioglitazone (10 μmol/L) or ± a liver receptor homolog 1 (LRH-1) antagonist 1-(3′-[1-(2-[4-morpholinyl]ethyl)-1H-pyrazol-3-yl]-3-biphenylyl)ethanon (1–10 μmol/L). Results: In fructose-, fat-, and/or cholesterol-rich diet–fed mice the development of fatty liver and the beginning of inflammation were associated with significantly lower hepatic phosphatidylcholine levels when compared with controls. Supplementing phosphatidylcholine significantly attenuated the development of fatty liver and inflammation, being associated with protection against the induction of PPARγ2, and activation of nuclear factor of κ light polypeptide gene enhancer in B-cell inhibitor α whereas Lrh1 expression was unchanged. The protective effects of phosphatidylcholine on the lipopolysaccharide-induced activation of J774A.1 cells and human monocytes were attenuated significantly by the PPARγ activator pioglitazone and the LRH-1 antagonist. Conclusions: Our data suggest that phosphatidylcholine levels in the liver are lower in early metabolic dysfunction–associated steatohepatitis in mice and that supplementation of phosphatidylcholine can diminish the development of metabolic dysfunction–associated steatotic liver disease through mechanisms involving LRH-1/PPARγ2/ nuclear factor κ-light-chain enhancer of activated B-cell signaling.

Esta contribuição discute a evidente virada à direita do cenário partidário austríaco, que se tornou clara nas eleições nacionais de 15 de outubro de 2017. Um processo de normalização, assim se pressupõe, condiciona uma adaptação à agenda parcialmente de extrema direita dos partidos populistas e leva a um foco na política de migração e de refugiados. Na tentativa de definir claramente o fenômeno “populismo de direita”, será ilustrada em detalhes a “destabuização” sem vergonha de conteúdo e declarações de extrema direita antes tabuizados, tomando como exemplo a aproximação entre o novo Partido Popular Austríaco (ÖVP) e o Partido Austríaco da Liberdade (FPÖ).

Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts.

The obituary of Dr. James Rankin highlights his significant contributions to the field of alcohol and other drugs over a career spanning 60+ years. Dr. Rankin's work focused on developing effective prevention and treatment services for individuals with alcohol and drug problems. His pioneering efforts included establishing the first clinic for alcohol-related problems in a large public hospital in Australia, conducting research, and advocating for evidence-based policies. Dr. Rankin's impact extended beyond Australia, as he also held key positions in Canada, contributing to clinical services, research, and policy development in the field. His legacy is honored through various awards, orations, and services named in his honor. [Extracted from the article]

Political egalitarians hold that there is a distinct ideal of political equality, which defines and justifies democracy. So what is political equality? The orthodox view says it is equality of opportunity for political influence, not equality of political influence. The first goal of this article is to argue against this view about the nature of political equality. From 1962 to 1983, Australia's First Nations citizens had the right to vote, but unlike other citizens they did not have the duty to vote. First Nations citizens were made politically unequal without being given any less opportunity for influence; the most plausible explanation for why they were made politically unequal is instead that they were made to exert less influence. The second goal is to use this challenge to illuminate the point of political equality. The orthodox view is typically undergirded by taking political equality to be concerned with some cosmic injustice that inheres in states of affairs, depending on the distribution of power. This is doubly mistaken. The point of political equality is deontic, not telic; and what it prescribes is not distributive, but relational. More specifically, the point of political equality is for the state to treat each citizen as an equal coauthor of the law. The overarching goal is to catalyze a more vigorous debate about political equality, akin to the long-standing debates about other dimensions of equality. [ABSTRACT FROM AUTHOR]

We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323-348. © 2016 Wiley Periodicals, Inc.